869P Prognostic impact of HPV ctDNA detection during chemoradiotherapy for cervix carcinoma

Abstract

Chemoradiotherapy (CRT) is the standard of care for patients diagnosed with locally advanced cervix carcinoma (LACC), a cancer caused by HPV infection. However, 30-60% of these patients develop local and/or distant relapse during follow-up. The objectives of this study were i) to design HPV droplet digital-PCR (ddPCR) assays for blood detection (including rare genotypes), and ii) to monitor blood HPV circulating tumor DNA (ctDNA) levels during CRT in patients with LACC. We retrospectively analysed blood samples from patients with HPV-positive non-metastatic LACC treated by a therapy sequence including radiation therapy. Patients were included when blood samples were available before CRT. HPV ctDNA detection was achieved using by genotype-specific ddPCR. For statistical analysis, Fisher exact test and LogRank tests were used. Forty-two patients were included. Tumor HPV typing detected HPV16, HPV18 or other genotypes (31, 35, 52, 58, 73) in respectively 64%, 21% and 14% of LACC. HPV ctDNA was detected before CRT in 27 of 42 patients (64%), and was correlated with tumor viral load (R=0.62, p<0.001). HPV ctDNA positivity for HPV18 (22%, n=2/9) was significantly lower than HPV16 (74%, n=20/27) or other genotypes (83%, n=5/6), p=0.011 (Chi-2). HPV ctDNA detection before CRT was not associated with tumor stage (Stage I: 46%, n=6/13 versus Stage II/III: 74%, n=21/29; p=0.16), but was associated with lymph node status (N0: 45%, n=9/20 versus N+: 82%, n=18/22, p=0.024). At baseline, HPV ctDNA detection status (+/-) or level (median HPV ctDNA copies/ml) had no significant prognostic impact on overall survival (p=0.46 and p= 0.64, respectively), nor on disease-free survival (p=0.81 and p=0.98, respectively). Among patients with blood collected at the end of the curative treatment (n=25), 2 (8%) displayed residual detectable HPV ctDNA. These two patients experienced a later relapse (at 6 and 42 months respectively). This study is the first to report detection of HPV ctDNA (before and after CRT) and its potential impact on survival in LACC. HPV ctDNA can be detected before CRT and becomes undetectable at the end of treatment, in most patients. Residual HPV ctDNA at the end of CRT could help identify patients more likely to later relapse.